Endothelial progenitor cells from human dental pulp-derived iPS cells as a therapeutic target for ischemic vascular diseases

• Published in: Biomaterials Vol. 34; no. 33; pp. 8149 - 8160
• Main Authors: Yoo, Chae Hwa, Na, Hee-Jun, Lee, Dong-Seol, Heo, Soon Chul, An, Yuri, Cha, Junghwa, Choi, Chulhee, Kim, Jae Ho, Park, Joo-Cheol, Cho, Yee Sook
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.11.2013
• Subjects: Advanced Basic Science; Animals; Cell Differentiation - physiology; Cells, Cultured; Dental Pulp; Dental pulp cells; Dentistry; Endothelial Cells - cytology; Endothelial progenitor cells; Flow Cytometry; Hindlimb - pathology; Humans; Induced Pluripotent Stem Cells - cytology; Inducible ischemia; Ischemia - therapy; Male; Mice; Myocardial infarction; Myocardial Infarction - therapy; Stem cell; Stem Cell Transplantation; Vascular Diseases - therapy; Inducible ischemia; Myocardial infarction; Stem cell; Dental pulp cells; Endothelial progenitor cells
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2013.07.001

Abstract Human dental pulp cells (hDPCs) are a valuable source for the generation of patient-specific human induced pluripotent stem cells (hiPSCs). An advanced strategy for the safe and efficient reprogramming of hDPCs and subsequent lineage-specific differentiation is a critical step toward clinical application. In present research, we successfully generated hDPC-iPSCs using only two non-oncogenic factors: Oct4 and Sox2 (2F hDPC-hiPSCs) and evaluated the feasibility of hDPC-iPSCs as substrates for endothelial progenitor cells (EPCs), contributing to EPC-based therapies. Under conventional differentiation conditions, 2F hDPC-hiPSCs showed higher differentiation efficiency, compared to hiPSCs from other cell types, into multipotent CD34+ EPCs (2F-hEPCs) capable to differentiate into functional endothelial and smooth muscle cells. The angiogenic and neovasculogenic activities of 2F-hEPCs were confirmed using a Matrigel plug assay in mice. In addition, the therapeutic effects of 2F-hEPC transplantation were confirmed in mouse models of hind-limb ischemia and myocardial infarction. Importantly, 2F-EPCs effectively integrated into newly formed vascular structures and enhanced neovascularization via likely both direct and indirect paracrine mechanisms. 2F hDPC-hiPSCs have a robust capability for the generation of angiogenic and vasculogenic EPCs, representing a strategy for patient-specific EPC therapies and disease modeling, particularly for ischemic vascular diseases.